1. Field of the Invention
The present invention relates to a method of manufacturing a triple cross-linked collagen. More specifically, the present invention relates to a method of manufacturing a triple cross-linked collagen with high melting point, low ratio of enzyme degradation, and high stability. The triple cross-linked collagen of the present invention can further be applied to long-term implant medical treatment.
2. Description of Related Art
Collagen can be widely found in the connective tissue, and collagen is also the elementary matrix for various human tissues such as bones, cartilages, ligaments, tendons, vessels, cornea, basement membranes, and skins. Moreover, because of the low immunological reactivity of collagen, collagen is widely applied in medical composition for treatment or tissue engineering to enhance the strength of tissues or to protect tissues.
However, it is found that many medical implants simply made of collagen-based materials are generally degraded in the body in a short time. Hence, most of the modern medical implants are made of cross-linked collagen with improved and stable structure instead of pure collagen.
Currently, the cross-linked collagen is made through either physical cross-linking reaction or chemical cross-linking reaction. Most of the time, physical cross-linking reaction for collagen is achieved by way of radioisotopes, UV radiation, or thermal dehydration. However, the cross-linked collagen obtained through physical cross-linking is apt to be destroyed, denatured, or degraded. Hence, physical cross-linking reaction is not a suitable method for manufacturing collagen for medical applications. On the other hand, the chemical cross-linking reaction of collagen is achieved through the application of cross-linking agent. is used to obtain the chemical cross-linking reaction. However, most of the residual cross-linking agents applied in the chemical cross-linking reaction for manufacturing cross-linked collagen is toxic for human body. In addition, owing to the disadvantages such as low melting point, and a high ratio of enzyme degradation, the cross-linked collagen manufactured by chemical cross-linking reaction hence is further limited to the application for temporary implants or very specific medical treatments. In fact, even though there are both amino functional groups and carboxylic functional groups in the collagen molecules, only the amino functional groups inside or between the collagen molecules react with each other in most chemical cross-linking reactions. Thus, uneven cross-linked collagen with low degree of cross-linking is frequently obtained through these chemical cross-linking reactions. Therefore, the resistance against enzyme degradation cannot be effectively improved.
In view of improving the problems illustrated above, a method of manufacturing a collagen with high degree of cross-linking to lower the rate of degradation, enhance the stability of collagen, and provide more choices for medical material is in strong demand.